The present invention relates to a veterinary composition in microencapsulated form useful for preventing and/or treating diarrhea or abortion, infections caused by gram-positive cocci and rods, anaerobic infections, rickettsial and chlamydial infections, and mycoplasma infections, More particularly it relates to a composition in the form of sustained release microcapsules to treat and prevent swine dysentery and containing erythromycin thiocyanate as active ingredient as well as a feedstuff containing said composition and a process for preparing the same.
It is known that by swine dysentery a common, important mucohemorrhagic diarrheal and exudative disease is meant, which occurs in most swine-producing countries. A spirochete, Treponema hvodvsenteriae, is the only agent involved in the transmission of swine dysentery, but other anaerobic bacteria that are normally present in the colon of pigs are necessary in addition to T. hyodvsenteriae to produce the disease in gnotobiotic pigs.
The disease is transmitted by ingestion of fecal material from affected or clinically normal swine caring T. hyodysenteriae. New outbreaks in herds from which the disease was previously absent usually follow the introduction of new stock. Once the disease has entered a herd, it usually spreads slowly at first, requiring close contact between pigs or the movement of relatively large amounts of infective feces. It may take several weeks or months to build up to a high morbidity. It remains permanently endemic and is difficult to eradicate. Any age of pig is susceptible but the incidence is highest between 15 and 17 kg. The incubation period is usually 7 to 14 days, but it may be considerably longer. In field cases the death rate in weanling pigs may be as high as 30% and the morbidity over 90% but in most cases the mortality is low and the morbidity about 25 to 50%.
The first evidence of the disease in most herds is the appearance of yellow-to-gray, soft feces combined with a slight reduction in appetite. As the disease progresses the feces may become watery, contain blood, mucus and a whitish mucofibrinous exudate, with staining of the perineal region; this leads to dehydration, weakness, emaciation, rough coat, incoordination and increased thirst. The body temperature may rise, however this is not consistent. The diffuse lesions are confined to the cecum, spiral colon, and rectum. In early stages, the affected mucosa is covered with a layer of transparent or gray mucus, often with suspended flecks of blood. More advanced cases have a a mixture of blood, fibrin, and necrotic debris adhered to the mucosal surface. Late in the course, yellow, necrotic debris is on the mucosal surface.
Where repopulation is impractical, the disease must be controlled by strict attention to hygiene, husbandry, prevention of stress and overcrowding and the judicious use of drugs. Several chemotherapeutic agents are useful as feed additives for the prophylaxis of swine dysentery; they include carbadox, lincomycin, arsanilic acid, virginiamycin, tylos in, and others. All these compounds must be used in conjunction with good husbandry and hygienic practices. They are most effective in keeping the disease subclinical, after the overt clinical signs have been controlled by water medication.
In recent years, however, for the treatment and prevention of many infections, and above all for swine dysentery, erythromycin thiocyanate has been strongly proposed. In comparison with tylosine and for example erytromycin estolate, erhythromycin thiocyanate has in fact the advantage to be an inexpensive material, so that its use would be of high interest thereby reducing the treatment costs.
Erythromycin is an antibiotic substance produced by a strain of Streptomyces ervthreus found in a soil sample from the Philippine Archipelago (U.S. Pat. No. 2,653,899 and 2,823,203 to Lilly and Abbott respectively). There are three erythromycins produced during fermentation, designated A, B and C; A is the major and most important component. Erythromyc in A and B contain the same sugar moieties, desosamine and cladinose. They differ in position 12 of the aglycone, erythronolide, A having an hydroxyl substituent. Component C contains desosamine and the same aglycone present in A but differs by the presence of mycatose instead of cladinose. In the above and following description, with erythromycin always erythromycin A is meant unless other specified.
However, the use of erythromycin thiocyanate as chemotherapeutic agent has not met with the consumers' approval. In fact, owing to its very unpleasant taste and smell, it is absolutely refused by all the animals having a developed olfactory and taste sense, such as for example pigs and fishes, dogs, cats, horses, etc.
Numerous attempts have been made to remove or mask erythromycin thiocyanate's unpleasant taste and to formulate a composition well accepted for example by pigs, but all efforts have proved unsuccessful. Surprisingly, It has now been found that by treating erythromycin thiocyanate with selected additives, a composition can be obtained that is suitable for preparing a feedstuff able to treat and/or prevent many infections in animals, particularly the swine dysentery.